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Lookup NU author(s): Rachel Roberts, Dr Sophie Weatherhead, Dika Pawitri, Dr Graham Smith, Dr Ashley RiderORCiD, Dr Henry Grantham, Dr Simon CockellORCiD, Professor Nick ReynoldsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Author(s)Ultraviolet B radiation (UVB) exerts pleiotropic effects on human skin. DNA damage response and repair pathways are activated by UVB; if damage cannot be repaired, apoptosis ensues. Although cumulative UVB exposure predisposes to skin cancer, UVB phototherapy is widely used as an effective treatment for psoriasis. Previous studies defined the therapeutic action spectrum of UVB and showed that psoriasis is resistant to apoptosis. This study aimed to investigate early molecular responses within psoriasis plaques following irradiation with single equi-erythemogenic doses of clinically-effective (311 nm, narrow-band) compared to clinically-ineffective (290 nm) UVB. Forty-eight micro-dissected epidermal samples from 20 psoriatic patients were analyzed using microarrays. Our bioinformatic analysis compared gene expression between 311 nm irradiated, 290 nm irradiated and control psoriasis epidermis to specifically identify 311 nm UVB differentially expressed genes (DEGs) and their upstream regulatory pathways. Key DEGs and pathways were validated by immunohistochemical analysis. There was a dynamic induction and repression of 311 nm UVB DEGs between 6 h and 18 h, only a limited number of DEGs maintained their designated expression status between time-points. Key disease and function pathways included apoptosis, cell death, cell migration and leucocyte chemotaxis. DNA damage response pathways, NRF2-mediated oxidative stress response and P53 signalling were key nodes, interconnecting apoptosis and cell cycle arrest. Interferon signalling, dendritic cell maturation, granulocyte adhesion and atherosclerotic pathways were also differentially regulated. Consistent with these findings, top transcriptional regulators of 311 nm UVB DEGs related to: a) apoptosis, DNA damage response and cell cycle control; b) innate/acquired immune regulation and inflammation; c) hypoxia/redox response and angiogenesis; d) circadian rhythmicity; f) EGR/AP1 signalling and keratinocyte differentiation; and g) mitochondrial biogenesis. This research provides important insights into the molecular targets of 311 nm UVB, underscoring key roles for apoptosis and cell death. These and the other key pathways delineated may be central to the therapeutic effects of 311 nm in psoriasis.
Author(s): Addison R, Weatherhead SC, Pawitri A, Smith GR, Rider A, Grantham HJ, Cockell SJ, Reynolds NJ
Publication type: Article
Publication status: Published
Journal: Redox Biology
Year: 2021
Volume: 41
Print publication date: 01/05/2021
Online publication date: 10/03/2021
Acceptance date: 26/02/2021
Date deposited: 19/04/2021
ISSN (electronic): 2213-2317
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.redox.2021.101924
DOI: 10.1016/j.redox.2021.101924
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